Beyond CAR T-Cell Therapy: Continued Monitoring and Management of Complications

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has recently emerged as a groundbreaking treatment for CD19-expressing hematologic malignancies and received rapid approval by the U.S. Food & Drug Administration. Tisagenlecleucel and axicabtagene ciloleucel are now widely available at CAR T-cell therapy centers around the United States. Many patients have achieved complete response or remission despite failing multiple previous lines of therapy, but some patients endure the severe risks of cytokine release syndrome, neurotoxicity, and other immunologic effects. As more patients receive this therapy, they will present to their primary oncologists in the community setting for continued follow-up. Oncology-trained advanced practitioners must then have a working knowledge of CAR T-cell therapy, its toxicities, and follow-up care. This review presents the CAR T-cell therapy development and infusion process with associated immediate management. In addition, patient assessment and disease monitoring, relevant diagnostics, unique grading systems to CAR T-cell therapy toxicities, indications for hospitalization, infection prophylaxis, and management of nonneutropenic and neutropenic fever are presented.

Case Report: Local Cytokine Release Syndrome in an Acute Lymphoblastic Leukemia Patient After Treatment With Chimeric Antigen Receptor T-Cell Therapy: A Possible Model, Literature Review and Perspective

“…CAR-T cell therapy has demonstrated inspiring efficacy in the treatment of B-cell original malignancies and its scope of application is broadening to many other malignancies even to solid cancers (2)(3)(4)(5)(6). Nevertheless, despite its promising efficacy, adverse events such as cytokine-release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenia and B-cell aplasia have limited the application of CAR-T cell therapy (7). Being one of the most common and severest adverse event, CRS is regarded as a systemic inflammatory reaction with constitutional manifestation such as fever and hyoxemia (8).…”

CT Demonstration of Local Cytokine-Release Syndrome Involving the Head and Neck Following Chimeric Antigen Receptor T Cell Infusion Therapy

“…There was no evidence of bacterial or viral infection in serological tests. These findings were classified as CRS grade 1 (the American Society for Transplantation and Cellular Therapy [ASTCT]) with localized inflammation [ 6 7 ]. Upon diagnosis of L-CRS based on clinical symptoms and elevated interleukin-6 levels, 10 mg of dexamethasone was immediately administered.…”

“…CAR-T cell infusion is a promising therapy for refractory ALL, and commonly results in complete response or remission among patients with various malignancies, including pediatric and adult ALL, non-Hodgkin’s lymphoma, and chronic lymphocytic leukemia unresponsive to standard therapies [ 6 ]. However, adverse events, such as CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), hemophagocytic lymphohistiocytosis, cytopenia, infection, and hypogammaglobulinemia, can limit the application of CAR-T cell therapy [ 7 ].…”

“…CRS is a clinical syndrome that initially presents with mild clinical symptoms such as fever, myalgia, and fatigue, which can worsen to severe CRS, characterized by life-threatening vasodilatory shock, hypoxia, electrolyte disturbance, coagulopathy, and end-organ dysfunction [ 6 8 ]. The ASTCT consensus includes grading scales from 1 to 5 to evaluate CRS according to the severity of fever, hypotension, and hypoxia [ 7 ]. CRS occurs in 58%–93% of patients after CAR-T cell therapy [ 9 ], and grade 3 or higher CRS is observed in 11%–47% of patients [ 8 9 ].…”

“…CRS occurs in 58%–93% of patients after CAR-T cell therapy [ 9 ], and grade 3 or higher CRS is observed in 11%–47% of patients [ 8 9 ]. The CAR-T cell therapy–associated TOXicity (CARTOX) Working Group noted that CRS is most likely to occur in the first 5 days after cell infusion [ 7 ]. It is necessary to differentiate infectious conditions based on the patient’s immune status.…”